title: Primary cervical carcinoma cell lines overexpress epithelial cell adhesion molecule (EpCAM) and are highly sensitive to immunotherapy with MT201, a fully human monoclonal anti-EpCAM antibody.
abstract: Epithelial cell adhesion molecule (EpCAM) is a surface glycoprotein highly differentially expressed in many epithelial malignancies. The goal of this study was to evaluate the expression of EpCAM and the potential of MT201 (adecatumumab), a human monoclonal antibody targeting EpCAM, against multiple primary cervical carcinoma cell lines.
  
  
  
  Epithelial cell adhesion molecule expression was evaluated by real-time polymerase chain reaction and flow cytometry in a total of 8 primary cervical cancer cell lines. Sensitivity to MT201-mediated cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested in standard 4-hour 51Cr release assays. To investigate the effect of interleukin-2 (IL-2) on MT201-mediated ADCC, 4-hour 51Cr release assays were also conducted in the presence of low doses of IL-2.
  
  
  
  High messenger RNA expression by real-time polymerase chain reaction and high EpCAM surface expression by flow cytometry were detected in 4 (50%) of 8 primary cervical carcinoma cell lines. With no exception, the primary cell lines derived from clinically aggressive tumors showed EpCAM overexpression. Whereas these cell lines were highly resistant to complement-dependent cytotoxicity and natural killer (NK)-dependent cytotoxicity in vitro (range of killing, 4%-19%), EpCAM-positive cell lines showed high sensitivity to MT201-mediated ADCC (range of killing, 23%-59%). Incubation with IL-2 in addition to MT201 significantly increased the cytotoxic activity against EpCAM-positive cervical cancer cell lines (P = 0.007). Addition of human serum also further increased the MT201-mediated killing of EpCAM-positive cell lines (P = 0.03).
  
  
  
  Epithelial cell adhesion molecule is highly expressed in primary cervical carcinoma cell lines, and these biologically aggressive tumors are highly sensitive to MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly effective treatment option for patients with cervical carcinoma, especially for those with advanced, recurrent, or metastatic disease refractory to standard salvage therapy.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Richter
authors.forename: Emiliano
authors.initials: E
authors.lastname: Cocco
authors.forename: Stefania
authors.initials: S
authors.lastname: Bellone
authors.forename: Marta
authors.initials: M
authors.lastname: Bellone
authors.forename: Francesca
authors.initials: F
authors.lastname: Casagrande
authors.forename: Paola
authors.initials: P
authors.lastname: Todeschini
authors.forename: Dominik
authors.initials: D
authors.lastname: Rüttinger
authors.forename: Dan-Arin
authors.initials: DA
authors.lastname: Silasi
authors.forename: Masoud
authors.initials: M
authors.lastname: Azodi
authors.forename: Peter E
authors.initials: PE
authors.lastname: Schwartz
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008875:Middle Aged; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C460839:adecatumumab